University of Texas Southwestern, Dallas, TX, USA; 8 Vancouver General Hospital, Vancouver, BC, Canada; 9

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1 First in Human Study with GSK285796, An Antibody Drug Conjugated to Microtubule-disrupting Agent Directed Against B-cell Maturation Antigen, in Patients with Relapsed/Refractory Multiple Myeloma: Results from Study BMA759 Part Dose Escalation Adam D. Cohen, Rakesh Popat 2, Suzanne Trudel, Paul G. Richardson 4, Edward N. Libby 5, Nikoletta Lendvai 6, Larry D. Anderson Jr 7, Heather J. Sutherland 8, Daren Austin 9, Stephen DeWall 9, Catherine E. Ellis 9, Zangdong He 9, Jolly Mazumdar 9, Catherine Wang 9, Joanna Opalinska 9, Peter M. Voorhees 0 Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA; 2 University College London Hospitals NHS Foundation Trust, London, UK; Princess Margaret Cancer Centre, Toronto, ON, Canada; 4 Dana-Farber Cancer Institute, Boston, MA, USA; 5 Seattle Cancer Care Alliance, Seattle, WA, USA; 6 Memorial Sloan-Kettering Cancer Center, New York, NY, USA; 7 University of Texas Southwestern, Dallas, TX, USA; 8 Vancouver General Hospital, Vancouver, BC, Canada; 9 GlaxoSmithKline, USA/UK; 0 Levine Cancer Institute, Carolinas HealthCare System, Charlotte, NC, USA

2 Background BCMA expression is restricted to B cells at later stages of differentiation and is requisite for the survival of long lived plasma cells BCMA is broadly expressed at variable levels on malignant plasma cells GSK is a humanized, afucosylated IgG anti-bcma antibody conjugated to a microtubule disrupting agent MMAF via a stable, protease resistant maleimidocaproyl linker Preclinical studies demonstrate its selective and potent activity BCMA x ADC BCMA Lysosome BCMA Malignant Plasma Cell Cell death BCMA Fc Receptor GSK ADCC Effector Cell Fc region of the Antibody Linker Drug Target specific Enhanced ADCC Stable in circulation MMAF (non cell permeable, highly potent auristatin ADC, antibody-drug conjugate; ADCC, antibody-dependent cell-mediated cytotoxicity; BCMA, B-cell maturation antigen; Fc, Fragment crystallizable; IgG, immunoglobulin G; MMAF, monomethyl auristatin-f Tai YT, et al. Blood 204;2(20):28-8. Mechanisms of Action:. ADC mechanism 2. ADCC mechanism. Immunogenic cell death 4. BCMA receptor signalling inhibition 2

3 First-in-Human Study of GSK285796: BMA759 Study Design Part : Dose escalation: N-CRM Bayesian model design Schedule *: escalating doses of GSK IV/60-min infusion once every weeks (2-day cycle) Maximum number of cycles: 6 Premedication requirements: prophylaxis steroid eye drops each dose Premedication for infusion reactions not permitted with first dose and not mandated at subsequent doses DLT assessment period: 2 days Intra-subject dose escalation permitted Primary objectives: Safety, tolerability, MTD, and recommended Phase 2/Part 2 dose Dose mg/kg Run in: Cohort size= until first drug-related Grade 2 toxicity *Schedule 2: weekly dosing was not investigated Part 2: Expansion (ongoing) Cohort : relapsed/refractory MM (n 40) Cohort 2: BCMA-positive relapsed DLBCL or follicular lymphoma (n 0).92 DLBCL, diffuse large B-cell lymphoma; DLT, dose-limiting toxicity; IV, intravenous; MM, multiple myeloma; MTD, maximum tolerated dose; N-CRM, continuous reassessment model Population: Patients with relapsed, refractory MM, who have undergone stem cell transplant, if eligible, received prior treatment with alkylators, proteasome inhibitors and immunomodulators and who have progression on, or within 60 days of completion of the last therapy

4 Part : Key Eligibility Criteria ECOG performance status 0 or Hematology: ANC >x0 9 /L Hemoglobin >8 g/dl PLTs >50x0 9 /L Coagulation: INR <.5 PTT <.5xULN Total bili.25xuln AST/ALT <.5xULN Serum creatinine <.2xULN or calculated creatinine clearance >60 ml/min Albuminuria <500 mg/24h LVEF >50% and troponin <xuln No current or history of corneal disease Note: BCMA expression not required for eligibility, and will be analyzed retrospectively on BM plasma cells ANC, absolute neutrophil count; ALT, alanine transaminase; AST, aspartate transaminase; bili, bilirubin; BM, bone marrow; ECOG, Eastern Cooperative Oncology Group; INR, international normalized ratio; LVEF, left ventricular ejection fraction; PLT, platelets; PTT, partial thromboplastin time; ULN, upper limit of normal 4

5 Part : Patient Status Enrollment by dose level N=0 Dose cohort 2 * GSK dose, mg/kg Patients enrolled, n *Cohort size > due to Grade 2 toxicity Treatment status Status, n (%) Ongoing Discontinued Reason for discontinuation, n (%) Disease progression Completed treatment (6 cycles) Adverse event N=0 0 () 20 (67) N=20 7 (85) (5) 2 (0) 5

6 Part : Baseline Patient and Disease Characteristics Characteristic Total population N=0 Age (years), median (min, max) 59.5 (9, 72) Females/males, % 4/57 5 prior lines*, n (%) 2 (70) IMiDs Lenalidomide Pomalidomide Thalidomide Refractory to IMiD Proteasome inhibitor Bortezomib Carfilzomib Refractory to PI 0 (00) 29 (97) 2 (77) 5 (50) 0 (00) 0 (00) 29 (97) 8 (60) 27 (90) Double refractory (IMiD/PI) 27 (90) Chemotherapy ASCT Daratumumab Refractory to Daratumumab High-risk genetics, n (%) del7p t(4:4) 28 (9) 20 (67) 5 (7) 4 () 7 (2) 6 (20) 2 (7) *One patient had missing data ASCT, autologous stem cell transplant; IMiD, immunomodulator; PI, proteasome inhibitor 6

7 Part : AEs Regardless of Relationship No DLTs Were Reported at Any Dose Level AEs reported in 20% patients, n (%) N=0 Any grade Grade * Any event 29 (97) 22 (7) Ocular Toxicity 6 (5) 2 (7) Nausea 5 (50) 0 Thrombocytopenia 5 (50) (4) Fatigue 4 (47) () Anemia 0 () 6 (20) Pyrexia 0 () 0 Chills 8 (27) 0 AST increased 6 (20) 0 Hypercalcemia 6 (20) (0) Neutropenia 6 (20) 4 () *No Grade 5 events reported Majority of AEs were Grade /2 and predicted 8/0 (27%) patients experienced IRR, chills was the most common symptom Grade ocular events: dry eye in patient improved; in another, limbal stem cell deficiency and blurred vision resolved AE, adverse event; IRR, infusion-related reactions

8 Part : Frequency of AEs of Interest by Dose Level Percentage IRR Ocular Toxicities Thrombocytopenia Dose, mg/kg 0.0, n= 0.06, n= 0.2, n=4 0.24, n=4 0.48, n=4 0.96, n=.92, n=4.4, n= 4.6, n=6 IRR reported across dose levels, occurred at first dose administration, all were Grade/2 Majority of ocular toxicities presented after first cycle, blurred vision and dry eyes were most common symptoms; majority were manageable with steroid and lubrication eye drops, and dose modifications Thrombocytopenia was transient 8

9 Part : AEs Leading to Dose Reductions, Delays or Treatment Discontinuation Dose level, mg/kg Number of enrolled patients AEs leading to dose delay n (%) AEs leading to dose reductions n (%) AEs leading to dose delay or dose reduction n (%) (25) 0 (25) 0.96 () () ().92 4 (75) 2(50) (75).4 (00) 2(67) (00) (50) 4 (67) 5 (8) The primary cause of GSK dose modifications was ocular toxicities (7/, 54%) followed by thrombocytopenia (/, 2%) AEs leading to study treatment discontinuation: One patient at the.92 mg/kg dose level discontinued due to Grade corneal toxicity (limbal stem cell deficiency) One patient at the 4.6 mg/kg dose level discontinued due to Grade hypercalcemia that was related to disease progression 9

10 Part : SAEs by Dose Level Part population, N=0 Dose (mg/kg) SAE Grade Relationship to GSK Hyperviscosity No 0.24 Hypotension 2 No Pyrexia No 0.48 Nausea 2 No Vomiting 2 No.92 Blurred vision; limbal stem cell deficiency Yes Spinal cord compression No.4 Pharyngeal hemorrhage No Pyrexia Yes 4.6 Pyrexia Yes Hypercalcemia No 9/0 (0%) patients experienced at least one SAE SAE, serious adverse event 0

11 Part : Pharmacokinetics and Immunogenicity Dose proportional exposure with 9-day half-life No accumulation on the once every weeks dosing regimen Unbound MMAF is 0.% of intact ADC concentrations BCMA receptor binding levels estimation: Engagement from 0.2 mg/kg Saturation from.92 mg/kg Free receptor recovery by Day 7 at higher dose levels No anti-drug antibodies detected at any dose level Concentration (ng/ml) 00 0 Dose mg/kg 0.2 mg/kg 0.48 mg/kg.92 mg/kg 4.60 mg/kg Data are preliminary Planned time (days) Patient numbers shown per data point mg/kg 0.24 mg/kg 0.96 mg/kg.40 mg/kg

12 Part : Serum sbcma Analyses Free sbcma and Complex ( drug-bound ) sbcma Free sbcma (ng/ml) Baseline free sbcma Part patients BMA 759 Part patients with MM Healthy donors Healthy donors All patients had detectable levels of free sbcma at baseline Free sbcma (ng/ml) Complex sbcma (ng/ml) Dose level 9: 4.6 mg/kg, n=6 Timepoint From dose level (0.2 mg/kg) to dose level 8 (.4 mg/kg), free and complex sbcma results show trends similar to dose level 9 Timepoint EOI, end of infusion; sbcma, soluble B-cell maturation antigen; SOI, start of infusion

13 Maximum % Change in M-Protein or Free Light Chain Maximum percentage change from baseline (PD) 0.96 (PD) 0.06 (SD) 0.2 (PD) 0.48 (SD) 0.2 (PD) 0.2 (SD) 0.2 (PD) 0.24 (SD) ORR = 8/0 (27%; 95% CI: 2.%, 45.9%) scr, VGPR, 4 PR CBR = /0 (7%; 95% CI: 9.9%, 56.%) 0.48 (SD).92 (SD) 4.60 (SD) 4.60 (SD).92 (SD).92 (MR) 0.24 (MR) 4.60 (MR) Dose, mg/kg (best unconfirmed response) 4.60 (PR) 4.60 (PR).40 (PR) 0.96 (PR) 4.60 (VGPR) Serum M-Protein Urine M-Protein Serum FLC.40 (VGPR).40 (scr).92 (VGPR) CBR, clinical benefit rate; CI, confidence interval; FLC, free light chain; M-protein, myeloma protein; MR, minimal response; ORR, overall response rate; PD, progressive disease; PR, partial response; scr, stringent complete response; SD, stable disease; VGPR, very good partial response

14 Part : Summary of Clinical Activity and Duration on Study Patients PD PD PD SD PD Missing Missing Missing Missing PD SD SD PD SD SD SD PR Cycle 8: increased to 0.48 SD MR Patient ongoing Patient completed 6 cycles Cycle : increased to 0.96 VGPR * MR *.92 mg/kg, n=2 ORR=9.5% 0.0 mg/kg 0.06 mg/kg 0.2 mg/kg 0.24 mg/kg 0.48 mg/kg 0.96 mg/kg.92 mg/kg.40 mg/kg 4.60 mg/kg SD PR MR scr VGPR PR.4 mg/kg, n=9 ORR= 66.7% VGPR PRSD Study treatment duration (days) 6 months 4

15 Conclusions GSK was well tolerated with no DLTs up to 4.6 mg/kg qw; MTD was not reached AEs were manageable with ocular toxicity emerging as the most frequent reason for dose modifications Hematologic toxicities such as thrombocytopenia and anemia are expected in the disease under study Thrombocytopenia emerged more frequently as treatment-related at higher doses; although events were transient and manageable 66.7% ORR including a stringent CR observed at higher doses of GSK in this refractory population.4 mg/kg was selected as the dose to investigate in the expansion phase of the study based on the totality of the data from Part Pharmacodynamic and correlative analyses are ongoing 5

16 Acknowledgments We wish to thank the participating site co investigators, research nurses, coordinators, supportive staff, and the GSK BMA759 study team We especially thank the patients and their families who participated in this study Study is funded by GSK; drug linker technology is licensed from Seattle Genetics Editorial support was provided by Katie White, PhD, at Fishawack Indicia Ltd, UK, and was funded by GSK Clinicaltrials.gov identifier: NCT